Regioselectivity in aromatic electrophilic substitution continues to attract chemical research even though the reaction is over 100 years old. The problem is this regioselectivity can be difficult to achieve. Take a monosubstituted arene, throw a chemical at it and see where it ends up. In a totally unspecific reaction the new substituent can occupy one of 3 different positions (ortho, meta or para) and with multiple substitutions the mix gets even more complicated. Regioselectivity can be introduced by so-called directing groups. Activating groups promote ortho and meta substitution and deactivating groups that of meta substitution. But what to do with them when the reaction is done?. An old trick that gets rediscovered from time to time is the use of a removable directing group. A classic is the sulfonic acid group in aromatic sulfonation or the carboxyl group. Recent case studies involving removable directing group are those on pyridyl silyl groups DOI, carboxyl groups DOI and cyano groups DOI.
A new route to an existing intermediate in the total synthesis of natural antibioticplatencimycin as reported by Magnus/Rivera/Lynch (Org. Lett. 2010). See previous posts here and here. As always in this type of work for each synthetic step many methods exist but only one will work as this report nicely illustrates.
In the animal world new species are discovered on a regular basis and the sighting of a rare species (the double tailed pigeon or purple Chichi-Sima tunicate) too may provoke media attention. So too in chemistry: David A. Lang et al. of Florida State University have stumbled on a rare sighting of the C34- anion of the carbide family and reports about it in the latest issue of JACS (DOI). The group's research actual target was a light-weight metal flux for use in alloys and as hydrogen storage material. A regular carbide is of the type MC2 such as calcium carbide with the carbon segment a deprotonated acetylide. The rare C3 fragment is called a sesquicarbide and can be found for example in Sc3C4. It can be regarded as a deprotonated allene.
The novel carbide (formally (Ca2+)2Li+(C3)4-(H-)) was synthesized by heating a mixture of calcium shot, lithium rod , carbon black and calcium hydride (10/10/6/1) at 1323 K. The product forms as 1 mm sized crystals in a Li/Ca melt that can be isolated by centrifugation. As expected in the solid state the C3 fragment is linear with C-C distance (132 pm) consistent with an allene. The calcium ions are present not only as an extension of the C3 unit but also perpendicular to it (pic). Lithium and hydrogen are present as alternating chains making it a double salt as in (Ca2C3)(LiH). Calcium and carbon alone will not form the C3 carbide. The new compound is oxidation prone and (violent) reaction with water yields allene itself.
The pun orgaNOmetallic chemistry in the intro text is courtesy of Nicholas Leadbeater who is discussing the merits of metal-free coupling reactions in an essay accompanying a research article by Sun et al. in Nature Chemistry (DOI). An earlier blog introduced Leadbeater advocating a metal-free Sonogashira reaction back in 2003. But these so-called metal-free reactions raise suspicions because minute quantities of metal may be present in any solvent or reagent , see for example the findings of Buchwald & Bolm in another blog. In his essay Leadbeater explains the preparations for the 2003 experiment were meticulous with an (unfortunate) student performing the reaction quarantined (but for how long!) in demetallized laboratory fitted with new glassware and fresh reagents. But when the lab moved from England to the US the reaction started to behave oddly and eventually traces (50ppb) of palladium were found lurking in the sodium carbonate.
Nevertheless Leadbeater fully supports the new Sun et al. research. They reacted bromoanisole with benzene (the solvent) in the presence of potassium tert-butoxide and a catalytic amounts of phenanthroline. Traces of Pd, Cu and Fe (10 ppb - 10 ppm) were found in the reagents using ICP-MS but deliberately adding these metals in larger quantities to the reaction did not improve conversion. They also had the reaction performed in other laboratories just to be sure.
Also in 2010 Liu et al. (DOI) used potassium tert-butoxide and another diamine N,N-dimethyl-ethylenediamine in a very similar reaction. Earlier in 2008 Yanagisawa et al. had already noted that nitrogen heterocycles could be coupled with just the base (DOI) In all reports the proposed mechanism is based on a aryl radical anion intermediate. In the Sun report the amine and butoxide base can be replaced by trusted radical initiators azobisisobutyronitrile and tributyltin hydride.